Management of critically ill children with acute necrotizing encephalitis during an H1N1 outbreak in a tertiary pediatric hospital: a series of three cases and literature review.

Acute necrotizing encephalopathy (ANE) is a severe neurologic condition that is diagnosed clinically and upon specific radiologic imaging. Medical treatment of this condition is uncertain, and timing is likely very important to minimize brain damage and systemic inflammation. The present case series describes three patients suffering from ANE secondary to influenza A/H1N1 infection during a recent outbreak, treated with increasingly aggressive anti-inflammatory approach, and with significantly different outcomes.

What Italian PICU Healthcare Providers Think About Donation After Cardiocirculatory Determination of Death: A National Survey.

BACKGROUND: Italy presently does not have a pediatric organ donation program after cardiocirculatory determination of death (pDCDD). Before implementing a pDCDD program, many centers globally have conducted studies on the attitudes of pediatric intensive care unit (PICU) staff. This research aims to minimize potential adverse reactions and evaluate the acceptance of the novel donation practice. METHODS: We conducted an electronic and anonymous survey on attitudes toward pDCDD among healthcare professionals (HCPs) working at eight Italian PICUs. The survey had three parts: (I) questions about general demographic data; (II) 18 statements about personal wishes to donate, experience of discussing donation, and knowledge about donation; (III) attitudinal statements regarding two pediatric Maastricht III scenarios of organ donation. RESULTS: The response rate was 54.4%, and the majority of respondents were nurses. Of those who responded, 45.3% worked in the Center, 40.8% in the North, and 12.8% in the South of Italy. In total, 93.9% supported pediatric organ and tissue donation, 90.3% supported donation after neurological determination of death (DNDD), 78.2% supported pDCDD, and 69.7% felt comfortable about the idea of participating in pDCDD on Type III patients, with a higher percentage of supportive responses in the Center (77.2%) than in the North (65.1%) and South (54.5%) of Italy (p-value < 0.004). Concerning scenarios, 79.3% of participants believed that organ retrieval took place in a patient who was already deceased. Overall, 27.3% considered their knowledge about DCDD to be adequate. CONCLUSIONS: Our study provides insight into the attitudes and knowledge of PICU staff members regarding pDCDD in Italy. Despite a general lack of knowledge on the subject, respondents showed positive attitudes toward pDCDD and a strong consensus that the Italian legislation protocol for determining death based on cardiocirculatory criteria respects the "dead donor rule." There were several distinctions among the northern, central, and southern regions of Italy, and in our view, these disparities can be attributed to the varying practices of commemorating the deceased. In order to assess how practice and training influence the attitude of PICU staff members, it would be interesting to repeat the survey after the implementation of a program.

Fluid assessment, fluid balance, and fluid overload in sick children: a report from the Pediatric Acute Disease Quality Initiative (ADQI) conference.

BACKGROUND: The impact of disorders of fluid balance, including the pathologic state of fluid overload in sick children has become increasingly apparent. With this understanding, there has been a shift from application of absolute thresholds of fluid accumulation to an appreciation of the intricacies of fluid balance, including the impact of timing, trajectory, and disease pathophysiology. METHODS: The 26th Acute Disease Quality Initiative was the first to be exclusively dedicated to pediatric and neonatal acute kidney injury (pADQI). As part of the consensus panel, a multidisciplinary working group dedicated to fluid balance, fluid accumulation, and fluid overload was created. Through a search, review, and appraisal of the literature, summative consensus statements, along with identification of knowledge gaps and recommendations for clinical practice and research were developed. CONCLUSIONS: The 26th pADQI conference proposed harmonized terminology for fluid balance and for describing a pathologic state of fluid overload for clinical practice and research. Recommendations include that the terms daily fluid balance, cumulative fluid balance, and percent cumulative fluid balance be utilized to describe the fluid status of sick children. The term fluid overload is to be preserved for describing a pathologic state of positive fluid balance associated with adverse events. Several recommendations for research were proposed including focused validation of the definition of fluid balance, fluid overload, and proposed methodologic approaches and endpoints for clinical trials.

Characteristics and outcomes of children ≤ 10 kg receiving continuous kidney replacement therapy: a WE-ROCK study.

BACKGROUND: Continuous kidney replacement therapy (CKRT) is often used for acute kidney injury (AKI) or fluid overload (FO) in children ≤ 10 kg. Intensive care unit (ICU) mortality in children ≤ 10 kg reported by the prospective pediatric CRRT (ppCRRT, 2001-2003) registry was 57%. We aimed to evaluate characteristics associated with ICU mortality using a contemporary registry. METHODS: The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) registry is a retrospective, multinational, observational study of children and young adults aged 0-25 years receiving CKRT (2015-2021) for AKI or FO. This analysis included patients ≤ 10 kg at hospital admission. PRIMARY AND SECONDARY OUTCOMES: ICU mortality and major adverse kidney events at 90 days (MAKE-90) defined as death, persistent kidney dysfunction, or dialysis within 90 days, respectively. RESULTS: A total of 210 patients were included (median age 0.53 years (IQR, 0.1, 0.9)). ICU mortality was 46.5%. MAKE-90 occurred in 150/207 (72%). CKRT was initiated at a median 3 days (IQR 1, 9) after ICU admission and lasted a median 6 days (IQR 3, 16). On multivariable analysis, pediatric logistic organ dysfunction score (PELOD-2) at CKRT initiation was associated with increased odds of ICU mortality (aOR 2.64, 95% CI 1.68-4.16), and increased odds of MAKE-90 (aOR 2.2, 95% CI 1.31-3.69). Absence of comorbidity was associated with lower MAKE-90 (aOR 0.29, 95%CI 0.13-0.65). CONCLUSIONS: We report on a contemporary cohort of children ≤ 10 kg treated with CKRT for acute kidney injury and/or fluid overload. ICU mortality is decreased compared to ppCRRT. The extended risk of death and morbidity at 90 days highlights the importance of close follow-up.

Pediatric AKI in the real world: changing outcomes through education and advocacy-a report from the 26th Acute Disease Quality Initiative (ADQI) consensus conference.

BACKGROUND: Acute kidney injury (AKI) is independently associated with increased morbidity and mortality across the life course, yet care for AKI remains mostly supportive. Raising awareness of this life-threatening clinical syndrome through education and advocacy efforts is the key to improving patient outcomes. Here, we describe the unique roles education and advocacy play in the care of children with AKI, discuss the importance of customizing educational outreach efforts to individual groups and contexts, and highlight the opportunities created through innovations and partnerships to optimize lifelong health outcomes. METHODS: During the 26th Acute Disease Quality Initiative (ADQI) consensus conference, a multidisciplinary group of experts discussed the evidence and used a modified Delphi process to achieve consensus on recommendations on AKI research, education, practice, and advocacy in children. RESULTS: The consensus statements developed in response to three critical questions about the role of education and advocacy in pediatric AKI care are presented here along with a summary of available evidence and recommendations for both clinical care and research. CONCLUSIONS: These consensus statements emphasize that high-quality care for patients with AKI begins in the community with education and awareness campaigns to identify those at risk for AKI. Education is the key across all healthcare and non-healthcare settings to enhance early diagnosis and develop mitigation strategies, thereby improving outcomes for children with AKI. Strong advocacy efforts are essential for implementing these programs and building critical collaborations across all stakeholders and settings.

Doppler-Derived Renal Functional Reserve in the Prediction of Postoperative Acute Kidney Injury in Patients Undergoing Robotic Surgery.

BACKGROUND: Postoperative acute kidney injury (PO-AKI) is a frequent complication after surgery. Various tools have been proposed to identify patients at high risk for AKI, including preoperative serum creatinine or estimated glomerular filtration rate (eGFR), urinary cell cycle arrest, and tubular damage biomarkers; however, none of these can appropriately assess AKI risk before surgery. Renal functional reserve (RFR) screened by the Doppler-derived intraparenchymal renal resistive index variation (IRRIV) test has been proposed to identify patients at risk for AKI before a kidney insult. IRRIV test has been developed in healthy individuals and previously investigated in cardiac surgery patients. This study aims to evaluate the value of the IRRIV test in identifying PO-AKI among patients undergoing robotic abdominal surgery in the Trendelenburg position for pelvic oncological disease. METHODS: We performed a prospective, double-blinded, observational study. Preoperative baseline renal function and RFR were assessed in 53 patients with baseline eGFR >60 mL/min/1.73 m2, undergoing robotic surgery in the Trendelenburg position for pelvic oncological disease. The capability of Doppler-derived RFR in predicting PO-AKI was investigated with the area under the receiver operating characteristic curve (ROC-AUC). RESULTS: Approximately 15.1% of patients developed AKI within the first 3 postoperative days. Thirty-one (58.5%) patients had a physiologic delta-RRI (ie, ≥0.05), while 22 (41.5%) patients did not. The ROC-AUC for PO-AKI was 0.85 (95% confidence interval [CI], 0.74-0.97; P = .007) for serum creatinine, 0.84 (95% CI, 0.71-0.96; P = .006) for eGFR, and 0.84 (95% CI, 0.78-0.91; P = .017) for delta-RRI. When combined with eGFR, the ROC-AUC for delta-RRI was 0.95 (95% CI, 0.9-1). CONCLUSIONS: Our findings show that the preoperative assessment of Doppler-derived RFR combined with baseline renal function improves the capability of identifying patients at high risk for PO-AKI with eGFR >60 mL/min/1.73 m2 after robotic abdominal surgery in Trendelenburg position for pelvic oncological disease.

Sampling from Extracorporeal Circuit: A Step Forward for Dose Monitoring in Continuous Renal Replacement Therapy.

INTRODUCTION: Continuous renal replacement therapies (CRRTs) require constant monitoring and periodic treatment readjustments, being applied to highly complex patients, with rapidly changing clinical needs. To promote precision medicine in the field of renal replacement therapy and encourage dynamic prescription, the Acute Dialysis Quality Initiative (ADQI) recommends periodically measuring the solutes extracorporeal clearance with the aim of assessing the current treatment delivery and the gap from the therapeutic prescription (often intended as effluent dose). To perform this procedure, it is therefore necessary to obtain blood and effluent samples from the extracorporeal circuit to measure the concentrations of a target solute (usually represented by urea) in prefilter, postfilter, and effluent lines. However, samples must be collected simultaneously from the extracorporeal circuit ports, with the same suction flow at an unknown rate. METHODS: The proposed study takes the first step toward identifying the technical factors that should be considered in determining the optimal suction rate to collect samples from the extracorporeal circuit to measure the extracorporeal clearance for a specific solute. RESULTS: The results obtained identify the low suction rate (i.e., 1 mL/min) as an ideal parameter for an adequate sampling method. Low velocities do not perturb the external circulation system and ensure stability prevailing pressures in the circuit. Higher velocities can be performed only with blood flows above 120 mL/min preferably in conditions of appropriate filtration fraction. DISCUSSION/CONCLUSIONS: The specific value of aspiration flow rate must be proportioned to the prescription of CRRT treatments set by the clinician.

Severe A(H1N1)pdm09 influenza acute encephalopathy outbreak in children in Tuscany, Italy, December 2023 to January 2024.

A severe outbreak of influenza A(H1N1pdm09) infection in seven children (median age: 52 months) occurred between December 2023 and January 2024 in Tuscany, Italy. Clinical presentation ranged from milder encephalopathy to acute necrotizing encephalopathy (ANE) with coma and multiorgan failure; one child died. This report raises awareness for clinicians to identify and treat early acute encephalopathy caused by H1N1 influenza and serves as a reminder of severe presentations of influenza in young children and the importance of vaccination.

Impact of the Magnitude and Timing of Fluid Overload on Outcomes in Critically Ill Children: A Report From the Multicenter International Assessment of Worldwide Acute Kidney Injury, Renal Angina, and Epidemiology (AWARE) Study.

OBJECTIVES: With the recognition that fluid overload (FO) has a detrimental impact on critically ill children, the critical care nephrology community has focused on identifying clinically meaningful targets for intervention. The current study aims to evaluate the epidemiology and outcomes associated with FO in an international multicenter cohort of critically ill children. The current study also aims to evaluate the association of FO at predetermined clinically relevant thresholds and time points (FO ≥ 5% and FO ≥ 10% at the end of ICU days 1 and 2) with outcomes. DESIGN: Prospective cohort study. SETTING: Multicenter, international collaborative of 32 pediatric ICUs. PATIENTS: A total of 5,079 children and young adults admitted consecutively to pediatric ICUs as part of the Assessment of the Worldwide Acute Kidney Injury, Renal Angina and Epidemiology Study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The FO thresholds at the time points of interest occurred commonly in the cohort (FO ≥ 5%Day1 in 38.1% [ n = 1753], FO ≥ 10%Day1 in 11.7% [ n = 537], FO ≥ 5%Day2 in 53.3% [ n = 1,539], FO ≥ 10%Day2 in 25.1% [ n = 724]). On Day1, multivariable modeling demonstrated that FO ≥ 5% was associated with fewer ICU-free days, and FO ≥ 10% was associated with higher mortality and fewer ICU and ventilator-free days. On multivariable modeling, FO-peak, Day2 FO ≥ 5%, and Day2 FO ≥ 10% were associated with higher mortality and fewer ICU and ventilator-free days. CONCLUSIONS: This study found that mild-to-moderate FO as early as at the end of ICU Day1 is associated with adverse outcomes. The current study fills an important void in the literature by identifying critical combinations of FO timing and quantity associated with adverse outcomes (FO ≥ 5%Day1, FO ≥10%Day1, FO ≥ 5%Day2, and FO ≥ 10%Day2). Those novel findings will help guide the development of interventional strategies and trials targeting the treatment and prevention of clinically relevant FO.

Standardization of Nomenclature for the Mechanisms and Materials Utilized for Extracorporeal Blood Purification.

In order to develop a standardized nomenclature for the mechanisms and materials utilized during extracorporeal blood purification, a consensus expert conference was convened in November 2022. Standardized nomenclature serves as a common language for reporting research findings, new device development, and education. It is also critically important to support patient safety, allow comparisons between techniques, materials, and devices, and be essential for defining and naming innovative technologies and classifying devices for regulatory approval. The multidisciplinary conference developed detailed descriptions of the performance characteristics of devices (membranes, filters, and sorbents), solute and fluid transport mechanisms, flow parameters, and methods of treatment evaluation. In addition, nomenclature for adsorptive blood purification techniques was proposed. This report summarizes these activities and highlights the need for standardization of nomenclature in the future to harmonize research, education, and innovation in extracorporeal blood purification therapies.

Monitoring anesthesia depth with patient state index during pediatric surgery.

BACKGROUND: Monitoring anesthesia depth in children is challenging. Pediatric anesthesiologists estimate general anesthesia depth using indirect methods such as pharmacokinetic models and neurovegetative reflexes. The application of processed electroencephalography may help to identify the correct anesthesia depth (i.e., patient state index between 25 and 50). AIMS: To determine the median values of patient state index and spectral edge frequency 95% in children undergoing general anesthesia conducted according to indirect evaluation of depth. The relationships between patient state index and spectral edge frequency 95% and indirect monitoring of anesthesia depth, type of anesthesia, age subgroups, and postoperative delirium were also assessed. METHODS: A prospective observational study on children (aged 1-18 years) undergoing surgery longer than 60 min. The SedLine monitor and the novel SedLine pediatric sensors (Masimo Inc., Irvine California) were applied. Patient state index levels were recorded for the duration of the anesthesia until the discharge to the ward at predefined time points. RESULTS: In the 111 enrolled children, median patient state index level at the end of anesthesia induction was 25 (22-32) and ranged from 26 (23-34) to 28 (25-36) in the maintenance phase. Patient state index at extubation was 48 (35-60) and 69 (62-75) at discharge from the operatory room. Median right/left spectral edge frequency 95% values at the end of induction were 10 (6-14)/9 (5-14) Hz and median right/left spectral edge frequency 95% values in the maintenance phase ranged from 10 (6-14) to 12 (11-15) Hz in both hemispheres. At extubation, right/left spectral edge frequency 95% levels were 18 (15-21)/17 (15-21) Hz. We observed 39 episodes of burst suppression in 20 patients (19%). Median patient state index levels were not different between patients undergoing inhalational and intravenous anesthesia and between those undergoing general anesthesia and general anesthesia added to locoregional anesthesia. Children <2 years displayed significantly higher patient state index levels than older patients (p = .0004). The presence of a burst suppression episode was not associated with PAED levels (OR 1.58, 95% CI 0.14-16.74, p` = .18). CONCLUSIONS: NonpEEG-guided anesthesia in children led to median patient state index levels at the low range of recommended unconsciousness values with frequent episodes of burst suppression. Patient state index levels were generally higher in children below 2 years.

Processed Electroencephalogram-Based Monitoring to Guide Sedation in Critically Ill Adult Patients: Recommendations from an International Expert Panel-Based Consensus.

BACKGROUND: The use of processed electroencephalography (pEEG) for depth of sedation (DOS) monitoring is increasing in anesthesia; however, how to use of this type of monitoring for critical care adult patients within the intensive care unit (ICU) remains unclear. METHODS: A multidisciplinary panel of international experts consisting of 21 clinicians involved in monitoring DOS in ICU patients was carefully selected on the basis of their expertise in neurocritical care and neuroanesthesiology. Panelists were assigned four domains (techniques for electroencephalography [EEG] monitoring, patient selection, use of the EEG monitors, competency, and training the principles of pEEG monitoring) from which a list of questions and statements was created to be addressed. A Delphi method based on iterative approach was used to produce the final statements. Statements were classified as highly appropriate or highly inappropriate (median rating ≥ 8), appropriate (median rating ≥ 7 but < 8), or uncertain (median rating < 7) and with a strong disagreement index (DI) (DI < 0.5) or weak DI (DI ≥ 0.5 but < 1) consensus. RESULTS: According to the statements evaluated by the panel, frontal pEEG (which includes a continuous colored density spectrogram) has been considered adequate to monitor the level of sedation (strong consensus), and it is recommended by the panel that all sedated patients (paralyzed or nonparalyzed) unfit for clinical evaluation would benefit from DOS monitoring (strong consensus) after a specific training program has been performed by the ICU staff. To cover the gap between knowledge/rational and routine application, some barriers must be broken, including lack of knowledge, validation for prolonged sedation, standardization between monitors based on different EEG analysis algorithms, and economic issues. CONCLUSIONS: Evidence on using DOS monitors in ICU is still scarce, and further research is required to better define the benefits of using pEEG. This consensus highlights that some critically ill patients may benefit from this type of neuromonitoring.

Diagnostic Agreement Between TEG5000 and TEG6S in the Assessment of Hemostasis in Pediatric Cardiac Surgery: A Prospective Non-inferiority Study.

Thromboelastography (TEG) is a point-of-care test (POCT) used to analyze the hemostatic properties of whole blood. TEG® 5000and TEG® 6s (Haemonetics Corp, USA) measure the same parameters describing clot viscoelasticity using different methodologies. The purpose of this study was to evaluate agreement between TEG5000 and TEG6s measurements. We analyzed prospectively collected tests resulting from paired blood samples in cardiac surgery pediatric patients at one hour (T0) and 24 h (T1) postoperatively. Each citrated sample was utilized for TEG® 5000 and TEG ®6s. Six specific TEG parameters were analyzed and compared: R kaolin time (RK), R kaolin heparinase (RKH) time, K kaolin time (KK), K kaolin heparinase time KH (KKH), Maximum Amplitude kaolin (MAK), Maximal Amplitude Kaolin Heparinase (MAKH). We enrolled 30 patients. Median (interquartile range) patients' age was 206 (20-597) days. All surgical patients underwent correction except 5 who were palliated. At T0, RK and RKH showed an average (standard deviation) % bias of 15.8 (31) and 16.1 (28), respectively, with similar results at T1. A % bias of -6 (23) and - 6 [15] in MAK was found at T0 and T1, respectively. Similarly, MAKH % bias was 1.5 (22) and 7.6 (29) at T0 and T1, respectively. At both timepoints, low % biases (< ± 6%) were demonstrated in KK and KKH. All parameters showed improved coagulation from T0 to T1, but without significant interaction between type of device and time. Analysis of the entire pool of 60 paired samples showed no agreement in diagnostic performance (within the range vs. outside the range) in 12 (20%), 5 (9.8%), 1 (1.7%), 4 (7.8%), 9 (15%), and 5 (9.8%) cases for RK, RKH, MAK, MAKH, KK and KKH, respectively. We observed substantial agreement in MAK and KK in a cohort of pediatric patients undergoing uncomplicated cardiac surgery. Our findings suggest that TEG®5000 and TEG®6s are interchangeable for assessing these parameters.

Fluid balance in pediatric critically ill patients (with and without kidney dysfunction).

PURPOSE OF REVIEW: The issues of fluid balance and fluid overload are currently considered crucial aspects of pediatric critically ill patients' care. RECENT FINDINGS: This review describes current understanding of fluid management in critically ill children in terms of fluid balance and fluid overload and its effects on patients' outcomes. The review describes current evidence surrounding definitions, monitoring, and treatment of positive fluid balance. In particular, the review focuses on specific patient conditions, including perioperative cardiac surgery, severe acute respiratory failure, and extracorporeal membrane oxygenation therapy, as the ones at highest risk of developing fluid overload and poor clinical outcomes. Gaps in understanding include specific thresholds at which fluid overload occurs in all critically ill children or specific populations and optimal timing of decongestion of positive fluid balance. SUMMARY: Current evidence on fluid balance in critically ill children is mainly based on retrospective and observational studies, and intense research should be recommended in this important field. In theory, active decongestion of patients with fluid overload could improve mortality and other clinical outcomes, but randomized trials or advanced pragmatic studies are needed to better understand the optimal timing, patient characteristics, and tools to achieve this.

Why is corneal donation so rare in children's hospices? A survey of multidisciplinary team members attitudes, knowledge, practice, and experience.

BACKGROUND: Corneal donation is a rare event among pediatric patients dying in children's hospices in Italy. Previous research suggests that lack of knowledge and negative attitude of Health Care Professionals (HCPs) are the most relevant factors for low donation rates in hospice, rather than patient ineligibility or public refusal. We conducted a national survey to explore children's hospice staff's knowledge and attitude toward corneal donation, to survey HCPs confidence in discussing the subject with patients and families, to investigate whether staff members receive specific training about corneal donation and its potential impact on the willingness to raise the topic with patients and families. METHODS: An anonymous web-based survey with multiple-choice responses was delivered to the team members of seven Italian children's hospices to test their knowledge and attitude about corneal donation. RESULTS: Of the seven children's hospices approached, four agreed to participate with a response rate of 48.5%. Among respondents, 70% declared that they had not received specific training about corneal donation. Results of statistical analysis showed that there were no significant differences in responses between trained and non-trained staff and among the different professionals (nurses, doctors, psychologists, AND social workers) regarding confidence in discussing the subject with patients and families. CONCLUSIONS: In our sample of HCPs working in Italian children's hospices, there was no difference in self-reported trust between professionals who reported receiving specific cornea donation training and those who did not. It is remarkable that training on corneal donation was endorsed by a minority of the sample.

Survival of infants treated with CKRT: comparing adapted adult platforms with the Carpediem™.

BACKGROUND: The most severely ill neonates and infants with AKI who need kidney replacement therapy have had to rely upon peritoneal dialysis, or adaptations of veno-venous continuous kidney replacement therapy (CKRT) devices for adults. Data from the Prospective Pediatric CRRT (ppCRRT) registry observed children < 10 kg had a lower survival rate than children > 10 kg (44% vs. 64%, p < 0.001). A CKRT device designed specifically for small children could improve outcomes. The Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM™) is specifically dedicated to providing CKRT for newborns and small infants. METHODS: We performed a retrospective cohort analysis comparing patient severity of illness and outcomes between the ppCRRT and CARPEDIEM registries, involving 6 Italian pediatric intensive care units. Thirty-eight subjects from the CARPEDIEM registry and 84 subjects from the ppCRRT registry < 10 kg were screened for comparison. We compared patient outcomes with a weight-matched cohort (< 5 kg) of 34 patients from the CARPEDIEM registry and 48 patients from the ppCRRT registry. RESULTS: The ppCRRT subjects had higher rates of vasoactive medication at CKRT initiation. Survival to CKRT termination was higher for CARPEDIEM subjects (33/34 vs. 21/48, p < 0.0001). Multivariable logistic regression showed that CARPEDIEM registry cohort was the only variable to retain an association with survival to CKRT discontinuation. CONCLUSIONS: We suggest children receiving CKRT using CARPEDIEM have excellent survival. Our data should be interpreted with caution given the retrospective comparison across two eras more than a decade apart.

Multisystem Inflammatory Syndrome in Children and Acute Kidney Injury: Retrospective Study of Five Italian PICUs.

OBJECTIVES: Multisystem inflammatory syndrome in children (MIS-C) manifests with heart dysfunction and respiratory failure some weeks after a severe acute respiratory syndrome coronavirus disease 2 infection. The aim of our study was to explore the prevalence, severity, timing, and duration of acute kidney injury (AKI) in MIS-C patients. Furthermore, we evaluated which clinical variables and outcomes are associated with AKI. DESIGN: Multicenter retrospective study. SETTING: Five tertiary hospital PICUs in Italy. Data were collected in the first 7 days of PICU admission and renal function was followed throughout the hospital stay. PATIENTS: Patients less than 18 years old admitted to the PICU for greater than 24 hours with MIS-C. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We collected the following data, including: demographic information, inflammatory biomarkers, lactate levels, Pa o2 /F io2 , ejection fraction, N-terminal pro-B-type natriuretic peptide (NT-proBNP), renal function (serum creatinine, urinary output, fluid balance, and percentage fluid accumulation), Vasoactive-Inotropic Score (VIS), pediatric Sequential Organ Failure Assessment (pSOFA), and Pediatric Index of Mortality 3. AKI was diagnosed in eight of 38 patients (21%) and severe AKI was present in four of eight patients. In all cases, AKI was present at PICU admission and its median (interquartile range) duration was 3.5 days (1.5-5.7 d). We did not identify differences between AKI and no-AKI patients when not making correction for multiple comparisons, for example, in weight, ejection fraction, pSOFA, Pa o2 /F io2 , and lactates. We failed to identify any difference in these groups in urine output and fluid balance. Exploratory analyses of serial data between no-AKI and AKI patients showed significant differences on lymphocyte count, NT-proBNP value, ejection fraction, pSOFA, Pa o2 /F io2 , and VIS. CONCLUSIONS: In this multicenter Italian PICU experience, MIS-C is associated with AKI in one-in-five cases. In general, AKI is characterized by an associated reduction in glomerular filtration rate with a self-limiting time course.

A Role of Circuit Clotting and Strategies to Prevent It during Blood Purification Therapy with oXiris Membrane: An Observational Multicenter Study.

INTRODUCTION: Membrane fouling is a significant complication potentially reducing clinical effects of extracorporeal blood purification (EBP) in critically ill septic patients with acute kidney injury. Although fascinating, the effect of heparin coating in preventing membrane fouling is currently unknown. This multicenter prospective study aims to preliminary describe the incidence, associated factors, and clinical consequences of premature circuit clotting in a cohort of adult critically ill septic patients treated with EBP using a high biocompatible heparin-coated hemodiafilter characterized by advanced adsorption properties. METHODS: This study was a retrospective analysis of prospectively entered data in the oXirisNet Registry; overall, 97 septic patients undergoing EBP with oXiris between May 2019 and March 2020 were enrolled in this study. Patients were divided into two groups according to the occurrence of filter clotting (premature vs. nonpremature). Logistic regression analysis was used to identify factors associated with premature circuit clotting. RESULTS: Premature clotting occurred in 18 (18.6%) patients. Results of the multivariate logistic regression analysis demonstrated that hematocrit (p = 0.02, odds ratio [OR] 1.15 [1.05; 1.30]), serum procalcitonin (PCT) (p = 0.03, OR 1.1 [1.05; 1.2]), and anticoagulation strategy (p = 0.05 at Wald's test) were independent predictors of circuit clotting. Systemic anticoagulation (p = 0.02, OR 0.03 [0.01; 0.52]) and regional citrate anticoagulation (p = 0.10, OR 0.23 [0.04; 1.50]) were both protective factors if compared to no-anticoagulation strategy. Patients with nonpremature circuit clotting showed more rapid recovery from hemodynamic instability, pulmonary hypo-oxygenation, and electrolyte disorders and greater improvement of inflammatory markers and SOFA scores. CONCLUSION: Although in this study the incidence of premature circuit clotting was relatively low (18.6%) compared to previously reported values (54%), membrane clotting in adult critically ill septic patients could cause clinically relevant interferences with treatment performances. Prevention of clotting should be based on avoiding higher patients' hematocrit, high serum PCT, and no-anticoagulation strategy which resulted as independent predictors of circuit clotting.

Acute Kidney Injury in Pediatric Cardiac Intensive Care Children: Not All Admissions Are Equal: A Retrospective Study.

OBJECTIVES: To describe the incidence, associated characteristics, and outcomes of the maximum severity of acute kidney injury (AKI) in a heterogeneous population of critically ill children with cardiac disease. DESIGN: Retrospective cohort study. SETTING: Pediatric cardiac intensive care unit (PCICU). PARTICIPANTS: Patients admitted to the PCICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: From January 2018 to July 2020 all patients admitted to a tertiary PCICU were included. Only the first admission was considered. Neonates ≤seven days old were excluded. Of 742 patients, 53 were medical cases, 69 catheterization laboratory cases, and 620 surgical cases (with five subgroups). The median age was 2.47 years (interquartile range [IQR], 0.38-9.85 years), with a median Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery score of 2 (IQR, 1-3). Median PCICU length of stay was three days (IQR, 2-7 days), and 21 (2.8%) patients died. Any incidence of AKI occurred in 70% of patients, 26% of which were classified as mild (stage 1) and 43% as severe (stages 2 and 3). AKI was diagnosed by urine output criteria in 56%, serum creatinine in 28%, and both in 16% of patients. Severe AKI occurred in subgroups as follows: medical (38%), catheterization laboratory (45%), correction (35%), palliation (55%), transplantation (85%), mechanical assistance (70%), and redo surgery (58%). Severe AKI patients were significantly older (p = 0.004), had a higher Pediatric Index of Mortality 3 score (p = 0.0004), had a higher cumulative fluid balance (p < 0.0001), and had a longer cardiopulmonary bypass time (p < 0.0001). Early AKI (≤24 hours from admission) was the most frequent presentation, with a greater proportion of severe cases in the early group compared with the intermediate (>24 and ≤48 hours) and late (>48 hours) (p < 0.0001) groups. Presentation of late severe AKI had a higher mortality (odds ratio, 4.9; 95% confidence interval, 1.8-15; p = 0.001). CONCLUSIONS: Severe AKI occurs in 43% of cardiac children and is diagnosed early, most often by urine output criteria. Severe AKI incidence varies significantly within subgroups of cardiac patients. Late AKI is associated with worse outcomes.

Vancomycin concentrations during cardiopulmonary bypass in pediatric cardiac surgery: a prospective study.

INTRODUCTION: Few data are available regarding intraoperative plasma concentrations of vancomycin administered as prophylaxis in pediatric cardiac surgery. The aims of this study were to investigate during pediatric cardiac surgery with cardiopulmonary bypass(CPB) the attainment of the area-under-the-curve of the vancomycin serum concentrations versus time over surgery to minimum inhibitory concentration ratio(AUCintra/MIC) of 400 (mg × h)/l and/or a target concentration of 15-20 mg/l. METHODS: In a prospective study, 40 patients divided into four subgroups (neonates, infants, children <10 years-old, ⩾10 years-old) undergoing cardiac surgery with cardiopulmonary bypass (CPB) were enrolled. A slow vancomycin bolus of 20 mg/kg, up to a maximum dose of 1000 mg was administered before skin incision and a further dose of 10 mg/kg (up to 500 mg) at CPB start. Vancomycin samples were collected intraoperatively at four time points. RESULTS: The median (interquartile range) age was 241.5 days (47-3898) and the median weight was 7.1 kg (3.1-37). The median AUCintra/MIC was 254.73 (165.89-508.06). In 11 patients the AUCintra/MIC target was not reached. Neonates displayed the lowest AUCintra/MIC values, and these were significantly lower than those of children ⩾10 years old (p = 0.02). Vancomycin concentrations were above the maximal target of 20 mg/l in 82.5% and 80% of patients at surgery and CPB start, respectively. At CPB and surgery end, 42.5% of patients showed vancomycin concentrations above 20 mg/l and 42.5% below 15 mg/l. Patients⩾10 years old showed the highest peak values whereas neonates were those with the lowest troughs. AUCintra/MIC correlated with age(r:0.36, p = 0.02), weight(r:0.35, p = 0.03), intraoperative protein value(r:0.40, p = 0.01), CPB priming volume/kg(r:-0.33, p = 0.04), CPB duration(r:0.36, p = 0.02) and vancomycin troughs(r:0.35, p = 0.04). CONCLUSIONS: An AUCintra/MIC ⩾400 target was not reached in one-quarter of children undergoing heart surgery. Vancomycin peaked before the start of surgery and neonates were those with the lowest troughs. Vancomycin concentrations are affected by CPB hemodilution and by patients' age and weight.